title: Blood glutathione redox status and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults.
abstract: Oxidative stress and DNA methylation are metabolically linked through the relationship between one-carbon metabolism and the transsulfuration pathway, but possible modulating effects of oxidative stress on DNA methylation have not been extensively studied in humans. Enzymes involved in DNA methylation, including DNA methyltransferases and histone deacetylases, may show altered activity under oxidized cellular conditions. Additionally, in vitro studies suggest that glutathione (GSH) depletion leads to global DNA hypomethylation, possibly through the depletion of S-adenosylmethionine (SAM). We tested the hypothesis that a more oxidized blood GSH redox status is associated with decreased global peripheral blood mononuclear cell (PBMC) DNA methylation in a sample of Bangladeshi adults. Global PBMC DNA methylation and whole blood GSH, glutathione disulfide (GSSG), and SAM concentrations were measured in 320 adults. DNA methylation was measured by using the [ (3)H]-methyl incorporation assay; values are inversely related to global DNA methylation. Whole blood GSH redox status (Eh) was calculated using the Nernst equation. We found that a more oxidized blood GSH Eh was associated with decreased global DNA methylation (B ± SE, 271 ± 103, p = 0.009). Blood SAM and blood GSH were associated with global DNA methylation, but these relationships did not achieve statistical significance. Our findings support the hypothesis that a more oxidized blood GSH redox status is associated with decreased global methylation of PBMC DNA. Furthermore, blood SAM does not appear to mediate this association. Future research should explore mechanisms through which cellular redox might influence global DNA methylation.
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Niedzwiecki
authors.forename: Megan N
authors.initials: MN
authors.lastname: Hall
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.forename: Julie
authors.initials: J
authors.lastname: Oka
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Harper
authors.forename: Vesna
authors.initials: V
authors.lastname: Slavkovich
authors.forename: Vesna
authors.initials: V
authors.lastname: Ilievski
authors.forename: Diane
authors.initials: D
authors.lastname: Levy
authors.forename: Alexander
authors.initials: A
authors.lastname: van Geen
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Mey
authors.forename: Shafiul
authors.initials: S
authors.lastname: Alam
authors.forename: Abu B
authors.initials: AB
authors.lastname: Siddique
authors.forename: Faruque
authors.initials: F
authors.lastname: Parvez
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Graziano
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
mesh_terms: D000328:Adult; D001459:Bangladesh; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005978:Glutathione / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012044:Regression Analysis; D018709:Statistics, Nonparametric
chemical_list: D006710:Homocysteine; D005978:Glutathione
keywords: DNA methylation; glutathione; glutathione disulfide; homocysteine; oxidative stress; peripheral blood mononuclear cells; redox